title: CD4+CD25+Foxp3+ regulatory T cells contribute in liver fibrosis improvement with interferon alpha.
abstract: The aim of this study is to investigate the optimal dose, treatment time, and possible immunologic mechanisms of interferon alpha (IFN-α) in the treatment of liver fibrosis. Mice were injected intraperitoneally with 10 % carbon tetrachloride to induce liver fibrosis, except in the normal control group. The experimental mice were randomly divided into four groups: physiological saline group, 20 U/gb wt IFN-α group, 40 U/gb wt IFN-α group, and 60 U/gb wt IFN-α group. After 3 and 6 weeks, type I collagen was detected in liver by hematoxylin and eosin (HE) stain, Masson's trichrome stain, and immunohistochemical staining. The number of CD8(+) T cells, the number of CD4(+)CD25(+)Foxp3(+) Tregs and the activation of CD4(+) T cells were detected in liver and spleen. Beneficial effects were observed in the 40 U/gb wt IFN-α group by pathological analysis. The number of CD8(+) T cells in the liver was significantly lower in mice receiving middle-dose IFN-α therapy as compared to mice receiving physiological saline (P < 0.05), while CD4(+)CD25(+)Foxp3(+) Tregs and activation of CD4(+) T cells in the liver were significantly higher in the therapeutic group than in the physiological saline group (P < 0.05). CD8(+) T cells (r = 0.3796) and activated CD4(+) T cells (r = 0.2437) were found to be positively correlated with the degree of liver fibrosis. CD4(+)CD25(+)Foxp3(+) Tregs (r = -0.7932) was found to be negatively correlated with the degree of liver fibrosis. IFN-α can inhibit liver fibrosis following 6 weeks of middle-dose IFN-α therapy by upregulating CD4(+)CD25(+)Foxp3(+) Tregs and suppressing CD8(+) T cells.
authors.affiliation: Department of Laboratory Medicine, The Second Hospital of Shandong University, 247#, Beiyuan Dajie, Jinan, 250033, China, fengpiaoluxu@163.com.
authors.forename: L
authors.initials: L
authors.lastname: Feng
authors.forename: H
authors.initials: H
authors.lastname: Kang
authors.forename: L N
authors.initials: LN
authors.lastname: Liu
authors.forename: Y M
authors.initials: YM
authors.lastname: Cao
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002251:Carbon Tetrachloride; D024042:Collagen Type I / Q000096:biosynthesis; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D016898:Interferon-alpha / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D024042:Collagen Type I; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016898:Interferon-alpha; D053645:Interleukin-2 Receptor alpha Subunit; D002251:Carbon Tetrachloride